1. Field of the Invention
The present invention relates to a microchip useful as a μ-TAS (Micro Total Analysis System) suitably used in a biochemical examination of DNA, protein, cell, immunity, blood and the like, chemical synthesis, as well as environmental analysis, and a method of using the same.
2. Description of the Background Art
Recently, in the fields of medical care and health, food product, drug discovery, and the like, the importance of sensing, detecting, and quantifying the biological material such as DNA (Deoxyribo Nucleic Acid) and enzyme, antigen, antibody, protein, virus, cells as well as chemical substance is increasing, and various biochips and micro-chemical chips (hereinafter collectively referred to as microchip) capable of easily and conveniently measuring the above have been proposed. As a series of experiments and analyzing operations performed in laboratories can be conducted in a chip of a few cm to 10 cm squares and about a thickness of a few mm to a few cm, the microchip has numerous advantages in that only a very small amount of specimen and reagent is necessary, the cost is low, the reaction speed is fast, a high throughput examination can be carried out, and the examination result can be immediately obtained at the specimen obtained site.
The microchip normally has a fluid circuit therein. The fluid circuit is mainly configured by, for example, each portion of a liquid reagent holding portion for holding a liquid reagent to mix or react with a specimen (blood by way of example), or to process the specimen, a measuring portion for measuring the specimen or the liquid reagent, a mixing portion for mixing the specimen and the liquid reagent, an optical measurement cuvette (detecting portion) for analyzing and/or examining the obtained mixed liquid, and a fine fluid path (e.g., fluid path having a width of about a few hundred μm) appropriately connecting each portion. The microchip is typically used by being mounted on a device (centrifugal device) capable of applying a centrifugal force thereto. The measurement and the mixing of the specimen and the liquid reagent, as well as, the introduction of the mixed liquid to the optical measurement cuvette can be carried out by applying the centrifugal force in an appropriate direction to the microchip. The examinations/analyses (e.g., detection of a specific component in the mixed liquid) of the mixed liquid introduced to the optical measurement cuvette (detecting portion) can be carried out by, for example, irradiating the optical measurement cuvette accommodating the mixed liquid with a detection light, and measuring the transmittance and the like thereof. The optical measurement cuvette accommodating the mixed liquid can be irradiated with the detection light from an angle substantially perpendicular to a surface of the microchip, and the like.
Thus, through the use of the microchip, the experiment, analysis and the like can be carried out with an extremely small amount of solution compared to the conventional experiment and analysis system using a pump, a pipette, a stirrer, and the like. However, since the handling amount of liquid is extremely small or less than or equal to a few tens μL in the experiments and the analyses using the microchip, a cross-sectional diameter of the optical measurement cuvette needs to be made small in order to perform the optical measurement of such small amount of liquid. In the conventional microchip, it is sometimes difficult to accurately align the optical measurement cuvette with an optical axis of the detection light. In particular, in the microchip where the liquid movement and the like in the fluid circuit is controlled using the centrifugal force, the microchip sometimes slightly move inside a microchip mounting portion of the centrifugal device due to the centrifugal force, and the above problem becomes significant. When using the centrifugal device in which a centrifugal force applying means and an optical measurement means are integrated, and a light source position itself cannot be moved, the alignment with the optical axis cannot carried out by fine tuning the light source position, and thus the microchip itself needs to have a structure capable of accurately aligning with the optical axis.
Furthermore, in the examinations and analyses using the microchip, especially the microchip capable of conducting examinations and analyses on plural items for one type of specimen introduced to the microchip (in this case, the microchip includes a plurality of optical measurement cuvettes), an easy and rapid detecting operation is desired to maximize the above merits of the microchip.
The centrifugal device (centrifugal force applying device) for applying the centrifugal force to the microchip normally includes a first circular stage that freely rotates (revolves) with a center point as the axis, where a microchip mounting portion composed of a groove having substantially the same shape as an outer shape of the microchip or a microchip fixing wall arranged along substantially the same shape as the outer shape of the microchip or the like is formed to incorporate the microchip on a surface of the first circular stage or on a surface of a second circular stage for rotating the microchip arranged on the first circular stage. After fitting the microchip into a region surrounded by the grooves or the walls, the first circular stage is rotated, and the centrifugal force is applied in an appropriate direction on the microchip while adjusting the orientation of the microchip by rotating the second circular stage as necessary.
It is very important to install the microchip in a correct orientation when fitting the microchip in the microchip mounting portion of the centrifugal device. If the microchip is fitted with the front and the back reversed, the liquid cannot be moved to the desired portion by the predetermined centrifugal operation. If the fluid path configuring the optical measurement cuvette (detecting portion) described above is not formed at a center position with respect to a thickness direction of the microchip, and is formed slightly shifted to the front or the back side of the microchip, the fluid path position and the light source position of the detection light shift if the microchip is fitted with the front and the back reversed, and the mixed liquid cannot be analyzed.
FIG. 26 is a schematic top view showing an outer shape of a conventional microchip described in Japanese Patent Laying-Open No. 2007-010435. As shown in FIG. 26, the conventional microchip has a symmetry plane A at the outer shape. If there is such symmetry plane or symmetry center, a problem in that the orientation (front and back etc.) of the microchip is easily mistaken arises when fitting the microchip to the centrifugal device. Further, the microchip is fabricated by laminating normally about two or three substrates, but a problem in that the orientation of the substrate tends to be easily mistaken arises when laminating the substrates in manufacturing the microchip.